Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
World J Gastroenterol. 2023 Feb 28;29(8):1315-1329. doi: 10.3748/wjg.v29.i8.1315.
Stress granules (SGs) could be formed under different stimulation to inhibit cell injury.
To investigate whether SGs could protect hepatocytes from hypoxia-induced damage during acute liver failure (ALF) by reducing endoplasmic reticulum stress (ERS) mediated apoptosis.
The agonist of SGs, arsenite (Ars) was used to intervene hypoxia-induced hepatocyte injury cellular model and ALF mice models. Further, the siRNA of activating transcription factor 4 (ATF4) and SGs inhibitor anisomycin was then used to intervene in cell models.
With the increase of hypoxia time from 4 h to 12 h, the levels of HIF-1α, ERS and apoptosis gradually increased, and the expression of SGs marker G3BP1 and TIA-1 was increased and then decreased. Compared with the hypoxia cell model group and ALF mice model, the levels of HIF-1α, apoptosis and ERS were increased in the Ars intervention group. After siRNA-ATF4 intervention, the level of SGs in cells increased, and the levels of HIF-1α, ERS and apoptosis decreased. Compared with the siRNA-ATF4 group, the levels of G3BP1 in the siRNA-ATF4+anisomycin group were decreased, and the levels of HIF-1α, ERS and apoptosis were increased. Moreover, compared with the ALF group, the degree of liver injury and liver function, the levels of HIF-1α, ERS and apoptosis in the Ars intervention group were decreased, the level of SGs was increased.
SGs could protect hepatocytes from hypoxia-induced damage during ALF by reducing ERS-mediated apoptosis.
应激颗粒（SGs）可以在不同刺激下形成，以抑制细胞损伤。
通过减少内质网应激（ERS）介导的细胞凋亡，研究 SGs 是否可以在急性肝衰竭（ALF）期间保护肝细胞免受缺氧诱导的损伤。
使用 SGs 的激动剂亚砷酸钠（Ars）干预缺氧诱导的肝细胞损伤细胞模型和 ALF 小鼠模型。进一步，用激活转录因子 4（ATF4）的 siRNA 和 SGs 抑制剂放线菌酮干预细胞模型。
随着缺氧时间从 4 小时增加到 12 小时，HIF-1α、ERS 和细胞凋亡水平逐渐增加，SGs 标志物 G3BP1 和 TIA-1 的表达先增加后减少。与缺氧细胞模型组和 ALF 小鼠模型组相比，Ars 干预组 HIF-1α、细胞凋亡和 ERS 水平升高。siRNA-ATF4 干预后，细胞中 SGs 水平增加，HIF-1α、ERS 和细胞凋亡水平降低。与 siRNA-ATF4 组相比，siRNA-ATF4+anisomycin 组 G3BP1 水平降低，HIF-1α、ERS 和细胞凋亡水平升高。此外，与 ALF 组相比，Ars 干预组肝损伤和肝功能程度、HIF-1α、ERS 和细胞凋亡水平降低，SGs 水平升高。
SGs 通过减少 ERS 介导的细胞凋亡，可保护 ALF 期间肝细胞免受缺氧诱导的损伤。
